Hunger and thirst both influence ingestion, but whether circuits underlying these states converge is unknown. Now, Gong et al. show that a population of glutamatergic neurons in the peri-locus coeruleus (periLC) respond during consumption of food or drink, and the responses of these cells are increased by palatability and in turn promote hedonic ingestion.
The authors used anterograde labelling and labelling of the immediate early gene product FOS to identify neurons downstream of hypothalamic agouti-related protein (AGRP) neurons, which encode hunger, and downstream of thirst-encoding neurons in the suprafornical organ (SFO). This approach identified neurons in the periLC.
The authors used optogenetics and chemogenetics to target periLC neurons expressing the glutamatergic marker vesicular glutamate transporter 2 (periLCVGLUT2 neurons). Chemogenetic inhibition of these cells increased food consumption by ad-libitum-fed mice during the light phase, when mice typically eat less. Optogenetic inhibition and activation of periLCVGLUT2 neurons while mice were in one of two connected chambers led to conditioned place preference or aversion for the paired chamber, respectively. Therefore, the activity of these cells is aversive and promotes food intake.
Next the authors used calcium imaging to assess the responses of periLC neurons during behaviour. In ad-libitum-fed mice, periLCVGLUT2 neurons selectively responded — by becoming more or less active — to eating food or drinking a palatable liquid food. Similar cell responses were also observed in water-restricted or food-restricted mice drinking water or eating a moderately palatable food, respectively. The size of the responses of most inhibited periLCVGLUT2 neurons and about two-fifths of activated periLCVGLUT2 neurons correlated with the duration of bouts of consumption and were greater in magnitude when the animal was hungry or thirsty. Moreover, inhibited neurons’ responses were sustained over the course of longer bouts, whereas a small fraction of activated periLCVGLUT2 neurons became inhibited over such bouts. Thus, periLCVGLUT2 neurons track the consumption of food and drink, and inhibited periLCVGLUT2 neurons could cause the length of consumption bouts to reduce as the animal becomes sated.
The periLCVGLUT2 neurons’ responses were scaled according to palatability, with smaller responses observed when animals consumed a diluted mixture of the palatable liquid food than when ingesting the non-diluted food. The authors tracked the neurons’ responses to different tastants (including bitter quinine and sweet sucrose). Different sets of activated periLCVGLUT2 neurons responded to tastants with opposite valences, whereas the same inhibited periLCVGLUT2 neurons responded to each of the different tastants, although with greater-magnitude responses to palatable than to less palatable tastants. These results suggest that activated and inhibited periLCVGLUT2 neurons may encode valence and palatability, respectively. Furthermore, photoinhibition of periLCVGLUT2 neurons when consuming a weak sucrose solution led to preference for this solution over a higher-concentration sucrose solution that was more palatable.
Experiments in which periLCVGLUT2 neurons were optogenetically inhibited during consumption or at non-contingent times revealed that reducing the activity of these cells only increased food or water intake when it was paired with consumption bouts. Photoinhibition of these neurons during consumption increased the duration of the bouts of consumption but did not affect the number of bouts.
“activated and inhibited periLCVGLUT2 neurons may encode valence and palatability, respectively”
Together, these results demonstrate that periLCVGLUT2 neurons increase consumption of palatable foods and drinks via a self-sustaining feedback cycle whereby consumption inhibits these neurons, which in turn promote further food or drink ingestion.
Gong, R. et al. Hindbrain double-negative feedback mediates palatability-guided food and water consumption. Cell https://doi.org/10.1016/j.cell.2020.07.031 (2020)
About this article
Cite this article
Bray, N. A taste for hunger and thirst. Nat Rev Neurosci 21, 592–593 (2020). https://doi.org/10.1038/s41583-020-00380-1